Introduction

Ethanol-induced gastric ulcers are common and the treatment options are limited. Escin, a extract from the horse chestnut plant, has been proven to have therapeutic effects in improving inflammation, edema, and vascular permeability. However, its effects and mechanisms on ethanol-induced gastric mucosal injury are not yet clear.

Aims & Methods

This study aims to explore the protective effect of Escin on ethanol-induced gastric mucosal injury and its potential mechanisms, providing a new drug choice for the treatment of ethanol-induced gastric ulcers. For this purpose, a control, ethanol, ethanol+Escin , and ethanol+omeprazole groups were established in male SD rats to compare and analyze the ulcer index and histopathological scores of each group. The network pharmacology approach was used to predict potential targets of Escin related to gastric ulcers. Apoptotic proteins, NF-κb inflammatory pathway proteins, inflammatory factors, and related mRNA expression were analyzed by methods such as Immunofluorescence (IF), Immunohistochemistry (IHC), Western Blot (WB), real-time quantitative fluorescence PCR (q-PCR), and enzyme-linked immunosorbent assay (Elisa). Furthermore, an ethanol-induced GES-1 cell injury model was established to evaluate the protective effect of Escin. Finally, Transcriptomic sequencing was performed to identify key regulatory genes.

Results

The study found that Escin significantly reduced the damage of ethanol to gastric mucosal tissues. Network pharmacology analysis predicted that Escin is closely related to inflammatory pathways such as NF-κb in the treatment of gastric ulcers. IHC and WB results showed that Escin reduced the loss of gastric mucosal surface markers MUC5AC, TFF2, and gastric mucosal barrier protein O-ccludin, inhibited the expression of inflammatory factors IL-1β, IL-6, TNF-α, and apoptosis-related proteins BAX, Caspase-3, and promoted the expression of anti-apoptotic protein BCL-2. IF further revealed that Escin prevented the nuclear translocation of NF-κb, thereby inhibiting the activation of the NF-κb pathway. Elisa results showed a decrease in inflammatory factor levels in the plasma of rats in the Escin group, while q-PCR results demonstrated that Escin downregulated the expression levels of inflammatory factor mRNA in gastric tissues. Cell proliferation experiments also confirmed the protective effect of Escin against ethanol-induced damage. Finally, Transcriptomic analysis revealed significant upregulation of 27 inflammation-related genes in ethanol-treated gastric tissues. Notably, nine genes—Birc3, Bcl3, SOCS1, SOCS3, Ccl2, Cx3cl1, Pim1, SGK1, and OSMR—were identified as positive regulators of the TNF-α/NF-κB signaling axis through functional annotation and pathway enrichment analysis.

Conclusion

Escin exerts a protective effect on ethanol-induced gastric mucosal damage by inhibiting the TNF-α/NF-κB pathway, reducing the expression of inflammatory factors and the level of cell apoptosis. Escin, as a novel therapeutic drug for ethanol-induced gastric ulcers, has certain clinical translational application value, but further clinical trials are needed to confirm the results.

Introduction

Post-liver transplant (LT) bile leaks (BLs) are successfully treated by endoscopic retrograde cholangiopancreatography (ERCP). While fully covered self-expandable metal stents (fc-SEMSs) have shown promising results, their use is often limited by concerns regarding adverse events (AEs), with limited data comparing their efficacy and safety. Moreover, European guidelines do not clearly endorse their up-front use over plastic stents. To date, no studies have directly compared these two treatments for post-LT BLs.

Aims & Methods

This study aims to compare the safety and efficacy of plastic versus fc-SEMS in treating post-LT BLs.
We conducted a retrospective study in single tertiary endoscopy center, reviewing cases from January 2018 to March 2024. Among 223 ERCPs performed in LT recipients, 30 patients treated with ERCP as first-line therapy for post-LT BLs were included. Patients with biliodigestive anastomosis dehiscence or prior interventions (percutaneous drainage or surgery) were excluded.

Results

Of the 30 patients (96.7% duct-to-duct anastomosis), 14 (46.7%) received plastic stents and 16 (53.3%) received fc-SEMSs. Anastomotic leaks were the predominant type (85.7% in the plastic stent group vs. 87.5% in the fc-SEMS group).Both groups achieved 100% technical and clinical success. No significant differences in AE rates were observed (42.9% for plastic vs. 37.5% for fc-SEMS, p=0.1), and no severe complications occurred. Among the 13 patients in whom biliary strictures (BSs) were reported, 4 cases were de novo strictures, occurring equally in the plastic stent group (n=2) and the fc-SEMS group (n=2). The remaining 9 strictures were present prior to BL treatment (3 in the plastic stent group and 6 in the fc-SEMS group). Resolution of BSs was achieved in 66.7% (4/6) of patients treated with fc-SEMSs, compared to 33.3% (1/3) in the plastic stent group, showing a borderline statistically significant difference (p=0.05), though this was limited by the small sample size. No patient required rescue procedures for persistent BL. A median of 2 ERCP sessions per patient (SD ±1) was needed for complete BL resolution. During a median follow-up of 8 months (IQR 1–27.3), only one recurrence occurred in the plastic stent group, successfully managed with fc-SEMS.

Conclusion

ERCP with either plastic stents or fc-SEMSs effectively treats post-LT BLs, with no significant differences in AEs between the two groups. Given their comparable success and safety, fc-SEMS could be considered not only as a rescue therapy but also as a primary, effective and safe treatment option.

References

1. Moy BT, Birk JW. A Review on the Management of Biliary Complications after Orthotopic Liver Transplantation. J Clin Transl Hepatol. 2019;7(1):61-71
2. Phillips MS, Bonatti H, Sauer BG, et al. Elevated stricture rate following the use of fully covered self-expandable metal biliary stents for biliary leaks following liver transplantation. Endoscopy. 2011;43(6):512-517
3. Dumonceau JM, Kapral C, Aabakken L, et al. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020;52(02):127-149

Clinical Case Summary

Celiac disease (CD), an autoimmune enteropathy triggered by gluten ingestion, commonly presents with gastrointestinal symptoms but can also manifest with various extra-intestinal symptoms, including cutaneous manifestations. Erythema nodosum (EN), a form of acute hypodermitis, is a rare extra-intestinal manifestation of CD and is often associated with other conditions such as infections and inflammatory enteropathies. We report the case of an 11-year-old girl who presented with erythema nodosum and was subsequently diagnosed with celiac disease. The patient exhibited deep, painful red nodules on the anterior surface of both legs and the dorsal surface of the feet, which persisted for a month prior to her referral. Laboratory testing revealed markers of celiac disease, and endoscopic evaluation revealed mosaic antritis and duodenitis with a characteristic fish-scale appearance. Duodenal biopsy confirmed a diagnosis of celiac disease (Marsh stage 3c class), with a significant intraepithelial lymphocytosis of 47%. After initiating a strict gluten-free diet, the patient showed complete resolution of the skin lesions within six weeks. This case underscores the importance of considering celiac disease in the differential diagnosis of erythema nodosum, particularly in patients with unexplained cutaneous manifestations. It also highlights the potential benefits of early screening for celiac disease in patients with EN, as a strict gluten-free diet can lead to both dermatological and gastrointestinal improvement. Further research is needed to establish a clear causal relationship between celiac disease and erythema nodosum.

Clinical Case Summary

Melioidosis, caused by Burkholderia pseudomallei, is an infectious disease endemic to tropical and subtropical regions. It poses a particular risk to immunocompromised individuals. This case report describes a 48-year-old male with Crohn's disease on biologic therapy who developed pulmonary melioidosis—a condition rarely reported among patients receiving biologics for inflammatory bowel disease.
A 48-year-old male, working as a plaster renderer in rural Queensland, presented with a productive cough, sore throat, fever, and night sweats. He had a background of Crohn’s disease and ankylosing spondylitis, managed with Adalimumab, mesalazine, and intermittent corticosteroids. He denied recent travel or gardening exposure.
Melioidosis was confirmed by positive cultures for Burkholderia pseudomallei from sputum and bronchial washings. Imaging demonstrated bilateral lower zone airspace opacities, a right-sided pleural effusion, and mediastinal lymphadenopathy, with CT features suggestive of a mass-like lesion in the right middle lobe bronchus. The overall picture was consistent with pulmonary melioidosis complicated by lymphadenopathy.
The patient received intravenous ceftazidime for four weeks, followed by oral trimethoprim-sulfamethoxazole for three months. Adalimumab was withheld during the acute infection, and he was managed with mesalazine (4.8 g daily) and prednisolone (20 mg daily) for his IBD.
Conclusion: In melioidosis-endemic areas, inflammatory bowel disease patients receiving biologic therapy can be safely managed if there is early recognition and prompt initiation of appropriate antimicrobial treatment. This case underscores the importance of maintaining a high index of suspicion for melioidosis in immunosuppressed patients presenting with respiratory symptoms in endemic regions.

References

1. Image of CT cross sectional image of right middle lobe mass

Clinical Case Summary

Introduction: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement, predominantly affecting the cardiovascular system. Aortic aneurysms and dissections are common complications. LDS shares features with other connective tissue disorders, such as Marfan and Ehlers-Danlos syndromes (1).
Case report: A 44-year-old male with a marfanoid habitus, history of thyroid carcinoma treated with radioactive iodine, appendectomy complicated by hematoma and dehiscence, and Loeys-Dietz syndrome type 3 (SMAD3 variant), diagnosed after a Stanford type A aortic dissection in 2022. In 2023, he underwent left carotid-subclavian bypass and ascending aortic aneurysm repair with hybrid graft. Family history included aortic dissection and hiatal hernia. He was on levothyroxine, dicoumarol, and omeprazole. Referred to the motility unit for preoperative evaluation of a large hiatal hernia seen on CT (Figure 1A).
He reported diet-related occasional nocturnal heartburn and regurgitation, well-controlled with PPIs. No dysphagia or alarm symptoms. Gastroscopy showed an 8–10 cm partially volvulated hernia sac without mechanical or vascular compromise. Esophagogram (1B) confirmed a mixed hiatal hernia with severe reflux and delayed esophageal clearance. High-resolution manometry with impedance (HRIM) showed a short esophagus (21 cm), ineffective motility, incomplete bolus transit and early post-swallow reflux (1C). Due to high risk of postoperative dysphagia, partial fundoplication was advised, but conservative management was chosen given prior surgical dehiscence and good symptom control.
Discussion: Gastrointestinal manifestations of LDS are rare and understudied. Large hiatal and abdominal wall hernias are among the most frequent findings, due to altered structural support at the esophagogastric junction (4,5). GERD symptoms are common and may require multidisciplinary care. HRIM is essential for preoperative planning in these patients.

References

1. Gouda, P., Kay, R., Habib, M., Aziz, A., Aziza, E., & Welsh, R. (2022). Clinical features and complications of Loeys-Dietz syndrome: A systematic review. International journal of cardiology, 362, 158–167. https://doi.org/10.1016/j.ijcard.2022.05.065
2. Wang, X. J., Babameto, M., Babovic-Vuksanovic, D., Bowen, J. M., & Camilleri, M. (2021). Audit of Gastrointestinal Manifestations in Patients with Loeys-Dietz Syndrome and Vascular Ehlers-Danlos Syndrome. Digestive diseases and sciences, 66(4), 1142–1152. https://doi.org/10.1007/s10620-020-06265-8
3. Honrubia Lopez, R., Burgos García, A., & Palacios Lázaro, E. (2017). Multiple perforation of small-intestine diverticula in a patient with Ehlers-Danlos syndrome. Revista espanola de enfermedades digestivas, 109(1), 83. https://doi.org/10.17235/reed.2016.4452/2016
4. Castori, M., Morlino, S., Pascolini, G., Blundo, C., & Grammatico, P. (2015). Gastrointestinal and nutritional issues in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. American journal of medical genetics. Part C, Seminars in medical genetics, 169C(1), 54–75. https://doi.org/10.1002/ajmg.c.31431
5. Thwaites, P. A., Gibson, P. R., & Burgell, R. E. (2022). Hypermobile Ehlers-Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know. Journal of gastroenterology and hepatology, 37(9), 1693–1709. https://doi.org/10.1111/jgh.15927

Introduction

Inflammatory Bowel Disease (IBD) patients carry a high risk of malnutrition, independently of disease activity. Screening for malnutrition in IBD is currently recommended since malnutrition, as well as low Fat-Free Mass Index (FFMI), have been associated to poor disease outcomes. However, due to a non-universal definition of malnutrition, most Nutritional Screening Tools (NSTs) have been validated compared to different reference methods and do not consider patients’ body composition. Moreover, the ability of most NSTs to predict malnutrition over time has not been explored.

Aims & Methods

The aim of this study was to compare the efficacy of different NSTs to predict malnutrition, as defined by the ESPEN 2015 and GLIM criteria, and a low FFMI in a cohort of inactive/mildly active IBD patients.
This is a prospective, single center, cohort study enrolling Crohn’s disease (CD) and ulcerative colitis (UC) patients in clinical remission or with mildly active disease as defined by Harvey-Bradshaw Index and partial Mayo Score, respectively. MUST, MIRT, MNA, NRS-2002 and SaskIBD-NR questionnaires and Bioelectrical Impedance Analysis (BIA) were performed at baseline and after six months follow-up. A low FFMI was defined as <18 kg/m2 in males and <15 kg/m2 in females. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of the different NSTs for the detection of malnutrition and low FFMI at six months were calculated.

Results

Sixty-six (CD: 32; UC: 34) IBD patients were enrolled. Median age was 55.5 years (IQR 34-62.8), median disease duration was 10 years (IQR 6-17). At baseline, all CD and 30/34 (88%) UC patients were in clinical remission; median C-reactive protein was 0.8 mg/L (IQR 0-3.8), median fecal calprotectin was 55.2 mcg/g (IQR 12.9-326). Of the entire cohort, 6/66 (9%) and 17/66 (26%) patients were malnourished according to GLIM and ESPEN criteria, respectively, [(GLIM CD:3, UC: 3)(ESPEN: CD: 3; UC:14)] and 5/66 (8%) had low FFMI (CD:1; UC: 4). At 6 months follow-up, all CD and 31/34 (91%) UC patients were in clinical remission. Ten out of 66 (15%) and 32/66 (48%) patients were malnourished according to GLIM and ESPEN criteria, respectively [(GLIM CD:5, UC: 5)(ESPEN: CD: 15; UC:17)], 11/66 (17%) patients had low FFMI (CD: 3; UC: 8). Baseline MIRT showed the highest sensitivity for the diagnosis of both ESPEN and GLIM-defined malnutrition at 6 months (ESPEN: 40.5%; GLIM: 50%). For ESPEN, MIRT and NRS2002 were the most accurate NSTs (MIRT: 50%, NRS2002: 51.5%), while SaskIBD (75.8%) showed the highest accuracy in detecting GLIM-malnourished patients at 6 months follow up. Among all NSTs, baseline MIRT, MNA and NRS2002 had the highest sensitivity for the detection of low FFMI at six months (MIRT, MNA, NRS2002: 45.5%), while SaskIBD_NR was the most accurate (80.3%).

Conclusion

MIRT might be the NSTs of choice to predict defined malnutrition and low Fat-Free Mass Index at 6 months follow-up in a cohort of inactive/mildly active IBD patients.

References

Huang S, Niu Y, Liu X, Gu Z, Huang A, Wu J. Characteristics of malnutrition according to Global Leadership Initiative on Malnutrition criteria in non-surgical patients with inflammatory bowel disease. Nutrition. 2022;94:111514. doi:10.1016/j.nut.2021.111514

Jensen GL, Cederholm T, Correia MITD, et al. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019;43(1):32-40. doi:10.1002/jpen.1440

Cederholm T, Bosaeus I, Barazzoni R, et al. Diagnostic criteria for malnutrition - An ESPEN Consensus Statement. Clin Nutr. 2015;34(3):335-340. doi:10.1016/j.clnu.2015.03.001

van Bokhorst-de van der Schueren MA, Guaitoli PR, Jansma EP, de Vet HC. Nutrition screening tools: does one size fit all? A systematic review of screening tools for the hospital setting. Clin Nutr. 2014;33(1):39-58. doi:10.1016/j.clnu.2013.04.008

Ding NS, Tassone D, Al Bakir I, et al. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis. 2022;16(9):1475-1492. doi:10.1093/ecco-jcc/jjac041